Search Results (110)

Atherosclerosis remains a leading cause of cardiovascular mortality despite advances in pharmacological and interventional therapies. Current treatment approaches face limitations including systemic side effects, inadequate local drug delivery, and restenosis following vascular interventions. Gel-based technologies offer unique advantages through tunable mechanical properties, controlled degradation kinetics, high drug-loading capacity, and potential for stimuli-responsive therapeutic release. This review examines gel platforms across multiple scales and applications in atherosclerosis research and intervention. First, gel-based in vitro models are discussed. These include hydrogel matrices simulating plaque microenvironments, three-dimensional cellular culture platforms, and microfluidic organ-on-chip devices. These devices incorporate physiological flow to investigate disease mechanisms under controlled conditions. Second, therapeutic strategies are addressed through macroscopic gels for localized treatment. These encompass natural polymer-based, synthetic polymer-based, and composite formulations. Applications include stent coatings, adventitial injections, and catheter-delivered depots. Natural polymers often possess intrinsic biological activities including anti-inflammatory and immunomodulatory properties that may contribute to therapeutic effects. Third, nano- and microgels for systemic delivery are examined. These include polymer-based nanogels with stimuli-responsive drug release responding to oxidative stress, pH changes, and enzymatic activity characteristic of atherosclerotic lesions. Inorganic–organic composite nanogels incorporating paramagnetic contrast agents enable theranostic applications by combining therapy with imaging-guided treatment monitoring. Current challenges include manufacturing consistency, mechanical stability under physiological flow, long-term safety assessment, and regulatory pathway definition. Future opportunities are discussed in multi-functional integration, artificial intelligence-guided design, personalized formulations, and biomimetic approaches. Gel technologies demonstrate substantial potential to advance atherosclerosis management through improved spatial and temporal control over therapeutic interventions. Full article

A multifunctional diagnosis and treatment carrier, ZIF-8@CDs, based on carbon quantum dots (CDs) and the zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework which serves as a core structure for constructing the responsive delivery platform, is developed in this paper. The anticancer drug doxorubicin (DOX) and Survivin oligo (siRNA) are loaded to form a ZIF-8@CDs/DOX@siRNA dual loading platform. CDs of 5–10 nm are synthesized by the solvent method and combined with ZIF-8. Electron microscopy shows that the composites are nearly spherical particles of approximately 200 nm, and the surface potential decreases from +36 mV before loading CDs to +25.7 mV after loading. The composite system shows unique advantages: (1) It has Fenton-like catalytic activity, catalyzes H₂O₂ to generate hydroxyl radicals, and consumes glutathione in the tumor microenvironment. The level of reactive oxygen species (ROS) in the ZIF-8@CDs group is significantly higher than that in the control group. (2) To achieve visual diagnosis and treatment, its fluorescence intensity is superior to that of the traditional Fluorescein isothiocyanate (FITC)-labeled vector; (3) It has a high loading capacity, with the loading amount of small nucleic acids reaching 36.25 μg/mg, and the uptake rate of siRNA by liver cancer cells is relatively ideal. The ZIF-8@CDs/DOX@siRNA dual-loading system is further constructed. Flow cytometry shows that the apoptosis rate of HepG2 cells induced by the ZIF-8@CDs/DOX@siRNA dual-loading system is 49%, which is significantly higher than that of the single-loading system (ZIF-8@CDs/DOX: 34.3%, ZIF-8@CDs@siRNA: 24.2%) and the blank vector (ZIF-8@CDs: 12.6%). The platform provides a new strategy for the integration of tumor diagnosis and treatment through the multi-mechanism synergy of chemical kinetic therapy, gene silencing and chemotherapy. Full article

The emergence of multidrug-resistant (MDR) bacterial pathogens has heightened the urgency for novel antibacterial agents. The bacterial cell wall usually comprises peptidoglycan, which presents a prime target for antibacterial drug development due to its indispensable role in maintaining cellular integrity. Conventional antibiotics such as β-lactams and glycopeptides hinder peptidoglycan synthesis through competitive binding of penicillin-binding proteins (PBPs) and sequestration of lipid-linked precursor molecules. Nevertheless, prevalent resistance mechanisms including target modification, β-lactamase hydrolysis, and multi-drug efflux pumps have limited their clinical utility. This comprehensive analysis explicates the molecular machinery underlying bacterial cell wall assembly, evaluates both explored and unexplored enzymatic nodes within this pathway, and highlights the transformative impact of high-resolution structural elucidation in accelerating structure-guided drug discovery. Novel targets such as GlmS, GlmM, GlmU, Mur ligases, D,L-transpeptidases are assessed for their inclusiveness for the discovery of next-generation antibiotics. Additionally, cell wall inhibitors are also examined for their mechanisms of action and evolutionary constraints on MDR development. High-resolution crystallographic data provide valuable insights into molecular blueprints for structure-guided optimization of pharmacophores, enhancing binding affinity and circumventing resistance determinants. This review proposes a roadmap for future innovation, advocating for the convergence of computational biology platforms, machine learning-driven compound screening, and nanoscale delivery systems to improve therapeutic efficacy and pharmacokinetics. The synergy of structural insights and cutting-edge technologies offers a multidisciplinary framework for revitalizing the antibacterial arsenal and combating MDR infections efficiently. Full article

Three-dimensional (3D) printing has transformed the development of microneedle arrays (MNAs) by enabling exceptional control over their geometry, distribution, materials, and functionality in a single-step, customizable process. This review represents a design-centric framework that organizes recent advancements in four interconnected levers: (i) individual microneedle (MN) geometry and size; (ii) patch-level MN distribution and multi-array architectures; (iii) computer-aided design (CAD), finite element analysis (FEA), computational fluid dynamics (CFD), and artificial intelligence/machine learning (AI/ML)-driven optimization; and (iv) manufacturing constraints and emerging solutions for scalability and reproducibility. Outcomes show that small changes in the radius of the MN’s tip, the MN’s aspect ratio, the MN’s internal lattice architecture, and the spacing of the array can dramatically influence their insertion force, mechanical reliability, payload capacity, and therapeutic coverage. Now, digital tools can bridge the design and experimental outcomes, while novel morphologies, hybrid materials, and theranostic integrations are expanding the clinical potential of MNs. The remaining challenges, resolution-versus-throughput trade-offs, biocompatibility, batch-to-batch consistency, and lack of testing standardization are examined alongside promising directions in high-throughput 3D printing, stimuli-responsive materials, and closed-loop systems. Finally, rational, model-guided design strategies are positioning 3D-printed MNAs as versatile platforms for painless, patient-specific drug delivery, diagnostics, and personalized medicine. Full article

Magnetic nanoparticles (MNPs) are widely applied in biomedicine, including bioimaging, drug delivery, and cell tracking. As central mediators of immune surveillance, macrophages phagocytize foreign substances, rendering their interactions with MNPs particularly consequential. During MNP uptake, macrophages undergo cytoplasmic remodeling that can lead to morphological alterations. Although prior studies have predominantly focused on MNP uptake efficiency and cytotoxicity, systematic quantitative assessments of macrophage morphological alterations following MNP treatment remain scarce. In this study, phase-contrast microscopy images of macrophages before and after MNP treatment were analyzed using unsupervised variational autoencoder (VAE)-based frameworks. Specifically, the β-VAE, β-total correlation VAE, and multi-encoder VAE frameworks were employed to extract latent representations of cellular morphology. The analysis revealed that MNP-treated macrophages exhibited pronounced structural alterations, including membrane expansion, central density shifts, and shape distortions. These findings were further substantiated through quantitative evaluations, including effect size analysis, kernel density estimation, latent traversal, and difference mapping. Collectively, these results demonstrate that VAE-based unsupervised learning provides a robust framework for detecting subtle morphological responses of macrophages to nanoparticle exposure and highlights its broader applicability across varied cell types, treatment conditions, and imaging platforms. Full article

Ultra-short peptides (USPs; ≤7–8 amino acids) emerge as minimal self-assembling building blocks for hydrogel-based biomaterials. Their intrinsic biocompatibility, straightforward synthesis, and ease of tunability make them particularly attractive candidates for potential use in bioprinting. This review provides an overview of the properties of USPs along with their applications in three-dimensional (3D) bioprinting. We first discuss how peptide sequence, terminal and side-chain modifications, and environmental triggers govern USPs’ self-assembly into nanofibers and 3D networks and how these supramolecular features translate into key rheological properties such as shear-thinning, rapid gelation, and mechanical tunability. We then survey reported applications in tissue engineering, wound healing, and organotypic models, as well as emerging ultra-short peptide-based systems for drug delivery, biosensing, and imaging, highlighting examples where printed constructs support cell viability, differentiation, and matrix deposition. Attention is given to hybrid and multi-material formulations in which USPs provide bioactivity while complementary components contribute structural robustness or additional functionality. Finally, this review outlines the main challenges that currently limit widespread adoption, including achieving high print fidelity with cytocompatible crosslinking, controlling batch-to-batch variability, and addressing the scalability, cost, and sustainability of peptide manufacturing. We conclude by discussing future opportunities such as AI-assisted peptide design, adaptive and multi-material bioprinting workflows, and greener synthetic routes, which together may accelerate the translation of ultra-short peptide-based bioinks from proof-of-concept studies to clinically and industrially relevant platforms. Full article

Tuberculosis (TB) remains a leading infectious killer, increasingly complicated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) disease; current regimens, although effective, are prolonged, toxic, and often fail to reach intracellular bacilli in heterogeneous lung lesions. This narrative review synthesizes how next-generation antimycobacterial strategies can be translated “from molecule to patient” by coupling potent therapeutics with delivery platforms tailored to the lesion microenvironment. We survey emerging small-molecule classes, including decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) inhibitors, mycobacterial membrane protein large 3 (MmpL3) inhibitors, and respiratory chain blockers, alongside optimized uses of established agents and host-directed therapies (HDTs). These are mapped to inhalable and nanocarrier systems that improve intralesional exposure, macrophage uptake, and targeted release while reducing systemic toxicity. Particular emphasis is placed on pulmonary dry powder inhalers (DPIs) and aerosols for direct lung targeting, stimuli-responsive carriers that trigger release through pH, redox, or enzymatic cues, and long-acting depots or implants that shift daily dosing to monthly or quarterly schedules to enhance adherence, safety, and access. We also outline translational enablers, including model-informed pharmacokinetic/pharmacodynamic (PK/PD) integration, device formulation co-design, manufacturability, regulatory quality frameworks, and patient-centered implementation. Overall, aligning stronger drugs with smart delivery platforms offers a practical pathway to shorter, safer, and more easily completed TB therapy, improving both individual outcomes and public health impact. Full article

Dynamic covalent hydrogels exhibiting multi-responsive and antibacterial properties offer significant potential for biomedical applications, including smart wound dressings and controlled drug delivery. Herein, a series of amphiphilic quaternized copolymers (Q-C8PEG-n) with tunable quaternization degrees was synthesized from C8PEG via iodomethane addition and characterized by ¹H NMR, COSY, FTIR, UV-vis spectroscopy, DLS, TEM, and zeta potential analyses, confirming successful quaternization and micelle formation. These copolymers displayed thermosensitive behavior, with cloud point temperatures increasing due to enhanced hydrophilicity. Q-C8PEG-3 micelles, incorporating diethanolamine units, were crosslinked with phenylboronic acid-grafted hyaluronic acid (HA-PBA) to yield dynamic covalent hydrogels (Gel) through reversible boronic ester bonds stabilized by B-N coordination. The Gel exhibited multi-responsiveness, undergoing degradation in acidic or alkaline conditions and exposure to glucose or H₂O₂. SEM confirmed a porous microstructure, enabling efficient drug encapsulation, as demonstrated by the release of Nile red (NR). In vitro antibacterial tests revealed enhanced post-quaternization efficacy, with the Gel showing strong activity against S. aureus. This micelle-crosslinked platform synergistically combines tunable stimuli-responsiveness with inherent antibacterial properties, holding promise for applications in wound healing and tissue engineering. Full article

The development of biohybrid micro-robots represents a groundbreaking advancement in targeted drug delivery for cancer therapy, offering unprecedented precision and reduced systemic toxicity. These microscale robots integrate synthetic materials with biological components such as bacteria, algae, red blood cells, or spermatozoa, capitalizing on the inherent motility, biocompatibility, and targeting capabilities of living organisms. This hybridization enables active navigation through complex biological environments, overcoming physiological barriers such as the blood–brain and endothelial junctions that impede traditional nanoparticle-based systems. In this study, we propose a multi-functional biohybrid micro-robotic platform composed of magnetically actuated synthetic chassis coated with doxorubicin-loaded lipid vesicles and tethered to Magnetospirillum magneticum for propulsion and tumor-homing capabilities. The results underscore the promise of biohybrid micro-robots as intelligent, minimally invasive agents for next-generation oncological therapies, capable of delivering chemotherapeutics with enhanced spatial and temporal accuracy. Future work will focus on clinical translation pathways, biosafety evaluations, and scalability of production under Good Manufacturing Practice (GMP) standards. Full article

The global incidence of multidrug-resistant (MDR) ESKAPE pathogens—comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species—has surged alarmingly in recent years, posing a significant challenge to healthcare systems worldwide. These organisms are notorious for their capacity to evade the effects of multiple classes of antibiotics, leading to treatment failures, increased morbidity and mortality, and escalating healthcare costs, all of which have placed unprecedented strain on existing infection control measures. This review encapsulates the progress in target-driven vaccine research, including the genomic discovery of highly conserved surface antigens, iron acquisition systems, biofilm- and quorum-sensing-related proteins, and computationally predicted epitopes, which are considered the most attractive targets for broad-spectrum vaccination. Novel vaccine platforms, such as outer membrane vesicles (OMVs), mRNA technologies, and multi-epitope constructs, will rapidly drive the translation of these targets into next-generation vaccine formulations. Nevertheless, challenges such as antigenic variation and immune evasion, as well as the need for a robust mucosal and cross-protective immune response, persist. The sustainability in interdisciplinary investigations are required, along with adjunctive measures and investment in the development of advanced discovery and delivery systems, to achieve the ultimate goal of successful vaccines against MDR ESKAPE infections and to mitigate the worldwide burden of antimicrobial resistance. Full article

Temperature-responsive hydrogels are sophisticated stimuli-responsive biomaterials that undergo rapid, reversible sol–gel phase transitions in response to subtle thermal stimuli, most notably around physiological temperature. This inherent thermosensitivity enables non-invasive, precise spatiotemporal control of material properties and bioactive payload release, rendering them highly promising for advanced biomedical applications. This review critically surveys recent advances in the design, synthesis, and translational potential of thermo-responsive hydrogels, emphasizing nanoscale and hybrid architectures optimized for superior tunability and biological performance. Foundational systems remain dominated by poly(N-isopropylacrylamide) (PNIPAAm), which exhibits a sharp lower critical solution temperature near 32 °C, alongside Pluronic/Poloxamer triblock copolymers and thermosensitive cellulose derivatives. Contemporary developments increasingly exploit biohybrid and nanocomposite strategies that incorporate natural polymers such as chitosan, gelatin, or hyaluronic acid with synthetic thermo-responsive segments, yielding materials with markedly enhanced mechanical robustness, biocompatibility, and physiologically relevant transition behavior. Cross-linking methodologies—encompassing covalent chemical approaches, dynamic physical interactions, and radiation-induced polymerization are rigorously assessed for their effects on network topology, swelling/deswelling kinetics, pore structure, and degradation characteristics. Prominent applications include on-demand drug and gene delivery, injectable in situ gelling systems, three-dimensional matrices for cell encapsulation and organoid culture, tissue engineering scaffolds, self-healing wound dressings, and responsive biosensing platforms. The integration of multi-stimuli orthogonality, nanotechnology, and artificial intelligence-guided materials discovery is anticipated to deliver fully programmable, patient-specific hydrogels, establishing them as pivotal enabling technologies in precision and regenerative medicine. Full article

Background: Antibiotic-loaded bone cement (ALBC) is widely used for local antibiotic delivery in joint arthroplasty to prevent and treat prosthetic joint infections (PJIs). In this study, we evaluated the efficacy of cemented Kirschner (K)-wires coated with various ALBC formulations using a Galleria mellonella infection model against multidrug-resistant (MDR) Staphylococcus aureus and Enterococcus faecalis. Methods: We tested commercially available bone cements, including gentamicin-only formulations (PALACOS R+G) and dual-antibiotic formulations, combining gentamicin with either clindamycin (COPAL G+C) or vancomycin (COPAL G+V), alongside an antibiotic-free control (PALACOS R). In vitro assays—including minimum inhibitory/bactericidal concentration (MIC/MBC) determination, antibiotic release kinetics, agar diffusion, and antibiofilm evaluations—demonstrated effective antibiotic release and significant antimicrobial activity against both planktonic and biofilm-associated bacteria. Results: In vivo, ALBC-coated K-wires were well tolerated in G. mellonella and significantly protected the larvae from S. aureus infection compared to controls. Notably, dual-antibiotic formulations provided superior protection, correlating with substantial reductions in bacterial colonisation on implant surfaces and in surrounding tissues. Conclusions: These findings support the utility of the G. mellonella model as a high-throughput, cost-effective platform for the preclinical evaluation of antimicrobial strategies to prevent and treat PJIs and further demonstrate the effectiveness of dual-loaded ALBC against multidrug-resistant bacteria. Full article

Chondroitin sulfate (CS)-based nanoparticles have emerged as versatile and multifunctional platforms for cancer therapy, integrating effective drug delivery with diagnostic capabilities. Their ability to exploit the enhanced permeability and retention (EPR) effect enables selective accumulation within tumor tissues, while surface modification with CS enhances targeting efficiency through strong conformational and electrostatic affinity for CD44 receptors, which are overexpressed in many cancer cells. In addition, CS interacts with E-selectin, providing dual-targeting capabilities superior to those of other polysaccharides such as hyaluronic acid. A wide variety of CS-derived nanostructures—including micelles, nanogels, hybrid liposomes, and CS–drug conjugates—have shown great potential not only in drug delivery but also in advanced therapeutic modalities such as photodynamic, sonodynamic, and immunotherapy. This review discusses recent advances (2020–2025) in CS-based nanoplatforms for cancer therapy, with particular emphasis on the role of CS within nanostructures. It highlights how the functionalization of nanoparticles with CS represents a powerful strategy to improve colloidal stability, pharmacokinetics, and receptor-mediated uptake, thereby enabling controlled, site-specific drug release and reducing off-target toxicity. Ultimately, these advances open new opportunities for cancer treatment, with the potential for bench-to-clinic translation through the integration of AI-guided design, organelle-specific targeting, multi-pathway modulation, and immune system engagement. Full article

Poly (lactic-co-glycolic acid) (PLGA) is a widely used copolymer with applications across medical, pharmaceutical, and other industrial fields. Its biodegradability and biocompatibility make it one of the most versatile polymers for nanoscale drug delivery. The present review addresses current knowledge and recent advances in PLGA-based co-delivery nanoformulations with a special reference to design strategies, functional mechanisms, and translational potential. Conventional and advanced fabrication methods, the structural design of PLGA-based nanocarriers, approaches to scale-up and reproducibility, classification of co-delivery types, mechanisms governing drug release, surface modification and functionalization are all discussed. Special attention is given to PLGA-based co-delivery systems, encompassing drug–drug, drug–gene, gene–gene and multi-modal combinations, supported by recent studies demonstrating synergistic therapeutic outcomes. The review also examines clinical translation efforts and the regulatory landscape for PLGA-based nanocarriers. Unlike most existing reviews that typically focus either on PLGA fundamentals or on co-delivery approaches in isolation, this article bridges these domains by providing an integrated, comparative analysis of PLGA-based co-delivery systems and elucidating a critical gap in linking design strategies with translational requirements. In addition, by emphasising the relevance of PLGA-based co-delivery for combination therapies, particularly in cancer and other complex diseases, the review highlights the strong clinical and translational potential of these platforms. Key challenges, such as reproducibility, large-scale manufacturing, and complex regulatory pathways, are discussed alongside emerging trends and future perspectives. Taken together, this review positions PLGA-based co-delivery strategies as a critical driver for advancing precision therapeutics and shaping the future landscape of nanomedicine. Full article

Background/Objectives: The ABCG2 transporter actively effluxes anticancer drugs, reducing their efficacy and promoting multidrug resistance (MDR). Developing oral formulations of poorly soluble ABCG2 inhibitors remains challenging due to their low solubility and intestinal permeability. This study aimed to formulate and evaluate an ABCG2 inhibitor using micro- and nanoscale drug delivery systems. Methods: To address the poor solubility and bioavailability of the corresponding active ingredient, a self-nanoemulsifying drug delivery system (SNEDDS) was developed. The SNEDDS was encapsulated into microcapsules using sodium alginate crosslinked with calcium chloride. Five microcapsule formulations were developed, varying in the inclusion of polyvinylpyrrolidone (PVP), Transcutol^® HP and SNEDDS. The effects of the excipients on encapsulation efficiency, swelling capacity, enzymatic stability, dissolution, cytocompatibility, and permeability were systematically evaluated. Results: The SNEDDS exhibited monodisperse particle sizes and efficient drug entrapment. Results revealed that formulations incorporating PVP and SNEDDS improved encapsulation efficiency and bioavailability. SNEDDS-containing formulations demonstrated superior enzymatic stability in simulated gastric and intestinal fluids and provided the highest cumulative drug release in vitro. Cytotoxicity studies conducted on Caco-2 and MCF-7 cells demonstrated that our formulations were well tolerated, indicating favorable biocompatibility. Conclusions: Our findings demonstrate that SNEDDS-loaded alginate microcapsules offer an efficient platform for oral delivery of dimeric ABCG2 inhibitors, combining enhanced solubility, stability, and controlled release. The optimized formulation can be regarded as a promising strategy to enhance the oral bioavailability of efflux pump inhibitors and other poorly soluble drugs. Full article